CYP8B1

CYP8B1, also known as sterol 12α-hydroxylase, is a member of the cytochrome P450 superfamily encoded by the CYP8B1 gene in humans. It is primarily expressed in the liver and localizes to the endoplasmic reticulum, where it catalyzes the 12α-hydroxylation step in the classic (neutral) bile acid synthesis pathway.

The enzyme participates in the formation of cholic acid, one of the major bile acids. By introducing a 12α-hydroxyl group on bile acid intermediates, CYP8B1 helps determine the relative amounts of cholic acid and chenodeoxycholic acid in the bile. The activity of CYP8B1 thus influences the composition of the bile acid pool, which in turn affects fat digestion and cholesterol metabolism. In models where CYP8B1 activity is reduced or absent, the bile acid pool shifts toward chenodeoxycholic acid, with downstream effects on lipid absorption and bile flow.

Biochemically, CYP8B1 is a heme-containing monooxygenase that relies on NADPH via the cytochrome P450 reductase for electron transfer to catalyze the hydroxylation reaction. Its expression and activity are integrated into the hepatic bile acid homeostasis network, being modulated as part of feedback mechanisms that regulate bile acid synthesis.

Clinical and genetic aspects include interest in how natural variants of CYP8B1 influence bile acid composition and susceptibility to gallstone formation or other metabolic conditions. Animal studies indicate that alterations in CYP8B1 can impact cholic acid production and related physiological processes, though the full extent of human clinical implications requires further research.